The proposed program is directed at the total synthesis of a wide range of biologically active mycotoxins and structurally related compounds. The synthetic strategies are chosen to provide efficient enantio- and stereoselective entries to target compounds. Our objective is to develop efficient synthetic methods which would allow the preparation of natural products and their various synthetic derivatives in significant quantities for biological testing. Specific target molecules include polyhydroxy indolizidine alkaloids, which act as potent glycosidase inhibitors; several Dendrobatid alkaloids, which provide invaluable tools for the investigation of ion transport in many biological systems; polyene mycotoxins of the citreoviridin family, which are potent inhibitors of oxidative phosphorylation; forskolin, which has been shown to activate adenylate cyclase and display a wide range of physiological effects; the seco acid of erythronolide A, and prostanoids. In particular, members of alkaloidal glycosidase inhibitors (i.e., swainsonine and castanospermine) are believed to be promising leads for the development of anticancer and antiviral agents. We anticipate that synthetic projects of verrucosidin and citreoviridin, which were initiated during the first three years of this grant, will be largely completed by the July 1, 1989 starting date requested in this application. This pivotal synthetic methodology to be utilized involves efficient stereoselection of prochiral sp2 sites by an allylic oxygen substituent. We believe a firm foundation has been laid for its application to natural product synthesis.